The studies as outlined in this proposal are a continuation of our studies on the regulation of cholesterol and bile acid formation in man with particular emphasis on the mechanism leading to the formation of cholesterol gallstones. Studies are being carried out related to the lipoprotein precursor source for cholesterol destined for biliary cholesterol and bile acids. The free cholesterol fraction of the lipoproteins appears to be the major precursor for cholesterol and bile acids and not esterified cholesterol. The studies suggest that the high density lipoprotein fraction is the principal lipoprotein fraction of plasma associated with the catabolism of cholesterol. It probably transports cholesterol from the tissues as free cholesterol to the liver. Low density lipoprotein cholesterol does not appear to be an efficient precursor source for bile acid or biliary cholesterol. Cholesterol esters as free cholesterol furnish only a small part (10% or less) of the cholesterol entering the hepatic biliary cholesterol and bile acid precursor compartments. It is planned to continue these lines of investigation by examining the kinetic relationships between the free and esterified cholesterol of various lipoprotein fractions in human subjects (with normal and intact enterohepatic circuits) administered precursors of cholesterol and labeled lipoproteins. Emphasis will be placed on the lipoprotein precursor source for bile acids and biliary cholesterol and the eventual application of the cholesterol model to patients with gallstones.